What is the association between Neurofibromatosis Type 1 (NF1) and lymphoma?

From the Guidelines

Patients with Neurofibromatosis 1 (NF1) are at an increased risk of developing malignant neoplasms, which may include lymphomas, although the provided evidence does not specifically quantify the risk of lymphoma in NF1 patients. The association between NF1 and malignant neoplasms, including potentially lymphomas, exists due to the mutations in the NF1 gene, which functions as a tumor suppressor by regulating the RAS pathway [ 1 ]. When this gene is dysfunctional, there is increased cell proliferation and reduced apoptosis, creating conditions favorable for malignant transformation.

Key Considerations for NF1 Patients

• NF1 affects approximately 1/1,900–1/3,500 people worldwide and is associated with an 8–15-year reduction in average life expectancy, primarily due to malignant neoplasms and cardiovascular causes [ 1 ].
• Common problems in patients with NF1 include malignant peripheral nerve sheath tumor (MPNST), breast cancer, cutaneous neurofibromas, and significant psychiatric and neurologic diagnoses [ 1 ].
• The management of NF1 patients, especially those with suspected lymphoma, should involve a multidisciplinary team including oncologists, neurologists, and geneticists to address both the potential lymphoma and the underlying NF1 condition.
• Regular surveillance is crucial for NF1 patients, including annual physical examinations and prompt investigation of any new or changing symptoms, with a higher index of suspicion for malignancies such as lymphoma [ 1 ].

Approach to Suspected Lymphoma in NF1 Patients

• Clinicians should be vigilant for signs and symptoms suggestive of lymphoma, such as persistent lymphadenopathy, unexplained fever, night sweats, or weight loss.
• While standard lymphoma treatment protocols may be followed, treatment may need to be modified based on individual patient factors and comorbidities associated with NF1.
• Evaluation by and care coordination with a specialized NF1 clinic is strongly encouraged for comprehensive management [ 1 ].

From the Research

Association between Neurofibromatosis Type 1 (NF1) and Lymphoma

• There is evidence to suggest a potential association between NF1 and lymphomas, with several case reports of lymphoma in patients with NF1 2, 3, 4, 5.
• The majority of studies support this association, although further investigation is needed to clarify the relationship between NF1 and lymphomas 3.
• NF1 patients have a well-known predisposition to certain types of malignancies, including malignant peripheral nerve sheath tumors, gliomas, and breast cancers, as well as a potential association with lymphoproliferative disorders such as lymphomas 3.
• The diagnosis of lymphomas, particularly cutaneous lymphomas, may be difficult in NF1 patients due to the presence of skin lesions and/or cutaneous/subcutaneous nodules or tumors like neurofibromas, which raises the possibility of underdiagnosed cutaneous lymphomas in NF1 patients 3.
• Different types of lymphoma have been reported in NF1 patients, including primary effusion lymphoma-like lymphoma 2, T-cell lymphoma 4, and non-Hodgkin's lymphoma 5.
• Treatment of lymphoma in NF1 patients may involve chemotherapy, with rituximab-containing chemotherapy potentially resulting in longer survival times than other regimens 2.